Biomimetic Immunosuppressive Exosomes that Inhibit Cytokine Storms Contribute to the Alleviation of Sepsis



Sepsis is a disease characterized by multiple organ  failure caused by immune hyperactivation and cytokine storms. Studies  have shown that the incidence of sepsis in melanoma patients is  substantially lower compared to the general population. It is also  observed that experimental tumor-bearing animals have high survival  rates after sepsis induction, suggesting that tumors may suppress  sepsis-associated immune overactivation, thereby alleviating sepsis.  Based on the above-described findings, this work assesses whether tumor  cells play an antisepsis role in mice through the secretion of exosomes.  Analysis of exosome activity reveals that the induced exosomes (iExo)  secreted by tumor cells following lipopolysaccharide (LPS) treatment  improve sepsis to a greater extent than normal secretory exosomes.  Further analysis reveals that iExo exert their protective effects mainly  through seven key miRNAs. In vitro bionic simulation of exosomes is  carried out using exosome mimics generated by loading the aforementioned  microRNAs into hyaluronic acid–polyethylenimine nanoparticles. Exosome  mimics at specific miRNA ratios alleviate sepsis in mice and cynomolgus  monkeys, indicating that biomimetic simulation of tumor-suppressive  exosomes may represent a promising therapeutic method for the treatment  of sepsis and cytokine-storm-related conditions.